Pellagra: a disease of tryptophan and niacin deficiency
Pellagra became common in Europe when maize was introduced from the New World as a convenient high-yielding dietary staple, and by the late nineteenth century it was widespread throughout southern Europe, north and south Africa, and the southern USA. The proteins of maize are particularly lacking in tryptophan, and as with other cereals little or none of the preformed niacin is biologically available.
Pellagra is characterized by a photosensitive der-matitis, like severe sunburn, typically with a butterfly-like pattern of distribution over the face, affecting all parts of the skin that are exposed to sunlight. Similar skin lesions may also occur in areas not exposed to sunlight, but subject to pressure, such as the knees, elbows, wrists, and ankles. Advanced pellagra is also accompanied by dementia (more correctly a depres-sive psychosis), and there may be diarrhea. Untreated pellagra is fatal.
The depressive psychosis is superficially similar to schizophrenia and the organic psychoses, but clini-cally distinguishable by sudden lucid phases that alternate with the most florid psychiatric signs. It is probable that these mental symptoms can be explained by a relative deficit of the essential amino acid tryp-tophan, and hence reduced synthesis of the neuro-transmitter 5-hydroxytryptamine (serotonin), and not to a deficiency of niacin per se.
Pellagra also occurs in India among people whose dietary staple is jowar (Sorghum vulgare), even though the protein in this cereal contains enough tryptophan to permit adequate synthesis of NAD. Here the problem seems to be the relative excess of leucine in the protein, which can inhibit the synthesis of NAD from tryptophan. It is likely that leucine is a factor in the etiology of pellagra only when the dietary intakes of both tryptophan and niacin are low, a condition that may occur when sorghum is the dietary staple, especially at times of food shortage.
Although the nutritional etiology of pellagra is well established, and tryptophan or niacin will prevent or cure the disease, additional factors, including defi-ciency of riboflavin or vitamin B6, both of which are required for synthesis of NAD from tryptophan, may be important when intakes of tryptophan and niacin are only marginally adequate.
During the first half of the twentieth century, of the 87 000 people who died from pellagra in the USA there were twice as many women as men. Reports of individual outbreaks of pellagra, both in the USA and more recently elsewhere, show a similar gender ratio. This may well be the result of inhibition of trypto-phan metabolism by estrogen metabolites, and hence reduced synthesis of NAD from tryptophan.
Several bacterial, fungal and environmental toxins activate ADP-ribosyltransferase or poly(ADP-ribose) polymerase, and it is possible that chronic exposure to such toxins will deplete tissue NAD(P) and hence be a contributory factor in the development of pella-gra when intakes of tryptophan and niacin are marginal.
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